We plan to investigate the effects of chronic treatment with despiramine and iprindole on the locus coeruleus-hippocampal system in the rat brain. More specifically, we plan to determine the effects of chronic tricyclic treatment on: (a) baseline electrical activity of locus coeruleus neurons; (b) receptor sensitivity of cell bodies in the locus coeruleus; (c) baseline electrical activity of hippocampal pyramidal cells; postsynaptic to locus coeruleus neurons; (d) receptor sensitivity of cell bodies in the hippocampal; pyramidal cells postsynaptic to locus coeruleus neurons. It is expected that these data can aid in determining the net effect of tricyclic drugs on NE systems. We also plan to repeat the same experiments on a locus-hippocampal system whose pathway has been either damaged by intracerebral injections of 6-hydroxydopmine or chronically stimulated.